Methamphetamine (METH) is a highly addictive drug of abuse that has been increasing in popularity in this country and around the world. Crystal METH is the drug of choice in Hawaii and is considered by far the most significant drug threat. Substance abuse increases risk taking behavior and as a result many victims of traumatic brain injury (TBI) are also using illicit drugs. Traumatic brain injury is also a significant public health problem in the United States and around the world with 1.5 million cases of TBI in this country each year. Both METH and TBI can independently cause direct toxicity to neurons as well as alter cerebral perfusion. This may lead to cellular distress and increased tissue injury. We propose to study the effect of METH use on cerebral perfusion, cerebral metabolism and neurologic outcome in patients with TBI. Our aims are 1) to evaluate the levels of cerebral N-acetyl aspartate (NAA) and lactate after TBI in subjects who test positive for METH as identified by toxicology testing (METH TBI) and in those who test negative for METH (non-METH TBI), using proton magnetic resonance (MR) spectroscopy, 2) to measure global and regional cerebral perfusion using quantitative magnetic resonance perfusion imaging (pMRI) in METH TBI versus non-METH TBI subjects, and 3) to assess cognitive outcome with neuropsychological testing at 6 months after injury in METH TBI versus non-METH TBI subjects. We hypothesize that 1) METH TBI subjects will display lower NAA and higher lactate levels in pericontusional tissue when compared to non-METH TBI subjects. These findings would provide evidence of increased cellular distress on proton MR spectroscopy. 2) METH TBI subjects will have lower pericontusional CBF when compared to non-METH TBI subjects. 3) METH TBI subjects will have increased neurobehavioral deficits when compared to non-METH TBI subjects. Very little is known about the synergistic effects of METH in patients with TBI. This study will help advance our understanding of the metabolic and hemodynamic changes that may lead to secondary brain injury and impact long term neurobehavioral recovery in patients who use METH prior to sustaining a TBI. The results of the proposed study will lead to a better understanding of the synergistic effects of METH abuse and TBI and may lead to new treatments for patients who present with these co-morbidities. In addition, these findings will be pertinent to public health and may help to inform public policy in the future. The proposed study will improve the understanding of the physiologic and functional consequences of methamphetamine use in patients who have suffered an acute traumatic brain injury. This will help inform public education and prevention efforts in this area. It may also allow the development of specific therapeutic strategies for this population of patients. [unreadable] [unreadable] [unreadable]